Organic primary or tertiary amines which contain a chiral center are usually prepared by synthetic methods which result in a racemic form of the compound. Frequently, biological properties of such compounds are associated primarily, and in some cases exclusively, with one of the possible enantiomers and, therefore, it is desirable and often necessary to resolve the racemate.
A frequently used method, among the known procedures for resolving racemates, employs the difference in properties between the diastereomeric salts obtained upon reaction of a racemic base with an optically active acid. Such procedure comprises mixing the racemate, in an appropriate solvent, with an optically active acid to form diastereomer salts; separating the diastereomers; and decomposing the separated salts to obtain the desired optical isomers of the racemic base.
There is a need for a resolving agent which (a) is suitable for use with the primary and tertiary asymmetric amines, and, particularly, primary and tertiary amines wherein the asymmetric carbon atom is attached directly to the amino group, (b) can be utilized in commercial processes, (c) can be regenerated economically and (d) can be reused.
Several optically active acids are widely employed in industry for this purpose, e.g., camphorsulfonic acid and tartaric acid. The recovery of the aforesaid resolving agents presents an economic problem since these agents are soluble in water and are, thus, difficult to recover. Thus, recycling operations are precluded, necessitating the use of fresh resolving agent for each run. Furthermore, the known resolving agents have limited applicability.
Another resolving agent of wide applicability which meets the desired criteria stated above is (-)-di-O-isopropylidene-2-keto-L-gulonic acid.